Published in the February 2006 issue of Today’s Hospitalist
When it comes to treating community-acquired pneumonia, hospitalists face a challenge: The best strategies to diagnose the disease and determine its etiology often leave you lacking the information you would like to make critical decisions.
Chest X-rays may be the gold standard for detecting infiltrates, but how many times have you treated patients for pneumonia with no radiologic sign of the disease? And while blood cultures can help you target therapy, they more often than not come up empty.
None of this is news to physicians, but several trends are compounding the challenges of diagnosing and treating pneumonia, particularly for patients who land in the hospital. One is the number of quality measures that require pneumonia patients to be treated quickly, often within four hours of admission. The other is the growth of drug-resistant organisms that shrug off your best guess at empiric therapy.
During the Fall 2005 Hospitalist CME Series, which was held in cooperation with Today’s Hospitalist magazine, Scott Flanders, MD, discussed the challenges of treating community-acquired pneumonia. And while Dr. Flanders, a nationally recognized authority on the condition, agreed that chest X-rays and blood cultures may not always give you all the information you need, he said there may be some good news.
When it comes to diagnostic strategies, for example, there are new tests on the horizon that may give physicians trying to diagnose pneumonia more information. And with etiologic testing, he said, researchers are demonstrating that targeted approaches can dramatically increase both the specificity and sensitivity of commonly used etiologic strategies.
Related article: New evidence on treating pneumonia
Interpreting chest X-rays
X-rays are often considered a key tool in diagnosing community- acquired pneumonia, but as every physician knows, their usefulness is often limited. Dr. Flanders, associate professor of medicine at the University of Michigan and director of the University of Michigan’s hospitalist program, cited several studies illustrating X-rays’ weakness in detecting pneumonia.
In one study, for example, investigators asked two radiologists to review chest films of patients who were thought to have pneumonia. Researchers found that even physicians trained in reading X-rays often couldn’t agree whether patients had an infiltrate.
“If the patient had COPD, the findings were discouraging,” Dr. Flanders said, “and the radiologists often couldn’t agree. The rate of agreement was a little better if there was no COPD.”
What’s more interesting, though, is that even when patients went on to develop a condition that was clearly pneumococcal pneumonia, the radiologists often couldn’t agree whether an infiltrate was visible on the film.
Dr. Flanders also pointed out that while both radiologists identified an infiltrate in only 15 of the study’s subjects, physicians treated most of the 250 patients for pneumonia.
“Clearly, the chest X-ray is not influencing our treatment decisions,” Dr. Flanders said. “Even radiologists are having a hard time agreeing on whether something is an infiltrate.”
No infiltrate on film
Other studies examining the usefulness of X-rays in diagnosing pneumonia have come up with similar results. The CAPITAL study, a landmark trial in which Canadian researchers examined the use of critical pathways in treating community-acquired pneumonia, paid particular attention to the role of chest X-rays.
When the CAPITAL study investigators examined all patients who had an admission and discharge diagnosis of pneumonia, they found that fully one-third did not have a clear infiltrate on X-ray. When they took a closer look at patients with seemingly negative X-rays who were thought to have pneumonia, however, investigators concluded these individuals were nearly as sick as patients who had an infiltrate on X-rays.
Dr. Flanders said that patients in the study with “negative” X-rays were about the same age as patients with clear evidence of an infiltrate on film. They also had a similar severity index, a similar rate of positive blood cultures, and similar mortality rates.
“What this is telling us is that a lot of patients are being admitted and managed as having pneumonia, yet they don’t have a positive X-ray,” Dr. Flanders explained. “But given the severity of illness we see in this group, they probably should be hospitalized.”
The meaning of a negative film
To get an idea of just how many cases of pneumonia chest films are missing, Dr. Flanders cited another study that compared chest X-rays to CT scans.
Researchers performed chest X-rays and CT scans on 50 patients diagnosed with pneumonia. While chest X-rays detected pneumonia in 18 patients, the CT scans detected a total of 26 cases of pneumonia, or eight more than the chest X-rays.
“This study shows that fully one-third of pneumonia in these patients was not found on chest X-rays,” Dr. Flanders explained. “Other studies, as well as anecdotal experience, suggest this is the case.”
The bottom line? While chest X-rays are a valuable tool in diagnosing pneumonia, they’re not perfect “and a negative film shouldn’t keep you from treating a patient for pneumonia.
“Realize that a positive chest X-ray is not mandatory to manage and treat patients as having pneumonia,” Dr. Flanders said. “Up to one-third of community-acquired pneumonia cases have very equivocal chest X-rays.”
One option: CRP testing
Because chest X-rays often don’t provide much help in diagnosing pneumonia, researchers have explored alternative tests, one of which is C-reactive protein, or CRP.
While you may think of CRP testing as the province of cardiologists, Dr. Flanders said that in Europe, the marker is regularly used to help diagnose patients with pneumonia. Guidelines from the British Thoracic Society, for example, recommend it for all hospitalized patients.
CRP is useful, Dr. Flanders said, because it reacts with c-polysaccharide in patients who have pneumococcal pneumonia. “It basically rises and falls with infection and tends to be stimulated much more by bacteria than viruses,” he explained. “It may help in differentiating etiology.”
While the test isn’t regularly used in the United States to diagnose pneumonia, Dr. Flanders said that the FDA recently approved a rapid finger stick assay for CRP. That has helped generate interest in the test as a marker for pneumonia.
Dr. Flanders also noted that he served as an investigator in a study that shed some light on CRP’s role as a marker of pneumonia. While that study showed that CRP identified more patients with pneumonia, Dr. Flanders said the marker was most helpful in diagnosing pneumonia when levels were at the extremes.
“You are about one-quarter as likely to have pneumonia if you have a very low CRP,” he explained, “and you have a 50-fold higher risk if your CRP is sky high.”
What do the results mean for practicing physicians? “You could make an argument that with extremely low CRP levels,” Dr. Flanders said, “perhaps we shouldn’t do an X-ray and we shouldn’t treat these patients. Conversely, with high CRPs, perhaps we should go ahead and treat independently of what the chest X-ray shows us.”
While Dr. Flanders said that the CRP study didn’t collect enough data to prove the above approach would work, he noted that a similar approach is used with other markers.
Other alternatives to X-rays
“¢ Procalcitonin. Like CRP, procalcitonin has shown promise in identifying patients with pneumonia because of its unique function. While procalcitonin levels rise when bacteria are present, Dr. Flanders said, they aren’t affected by the presence of rheumatologic diseases, as is the case with markers like CRP.
He cited a Swiss study that looked at the effects of a procalcitonin- based management algorithm on the care of pneumonia patients. Investigators found that when physicians gave antibiotics only to patients with high procalcitonin levels, they cut their antibiotic usage in half without compromising patient care.
While the results are promising, Dr. Flanders pointed out that the study was small, had many limitations and needs to be replicated.
“¢ s-TREM. A marker known as s-TREM, which stands for soluble triggering receptor expressed on myeloid cells, not only rises in the presence of bacterial infection, but increases with fungal infection. It does not, however, respond to viruses or non-infectious disorders, which may make it an excellent marker for pneumonia.
In one study cited by Dr. Flanders, s-TREM accurately differentiated patients who did and didn’t have infection. The marker was accurate even when patients had already begun receiving antibiotics.
The high cost of blood cultures
When it comes to determining the etiology of pneumonia, many of the most widely-used strategies like blood and sputum cultures provide little guidance. As proof, Dr. Flanders noted that no cause of pneumonia is found in nearly 60 percent of patients in the research setting and 75 percent of patients in community-based practices.
Blood cultures are a good example. While some research has shown improved outcomes in patients who receive blood cultures within 24 hours of admission, the reality is that in most cases, blood cultures are negative and rarely result in changes to antibiotics.
In the CAPITAL Study, for example, researchers found positive blood cultures in only 5 percent of about 1,000 patients hospitalized for pneumonia. An even smaller number of patients had their therapy affected by a positive blood culture.
Investigators found only three cases, in fact, in which a positive blood culture resulted in more reliable coverage. Because blood cultures so infrequently affected patient care, Dr. Flanders explained, researchers concluded that it cost nearly $2,000 to change one pneumonia patient’s therapy.
“That’s pretty underwhelming when you apply blood cultures to the whole population,” Dr. Flanders said.
Dr. Flanders said that the poor showing of blood cultures has led researchers to take a different tack. Some are questioning whether it makes sense to obtain blood cultures for all patients in whom pneumonia is suspected.
Taking a targeted approach
In another study, researchers identified several variables that can help predict when blood cultures are likely to be positive ” and helpful in targeting treatment for pneumonia.
Researchers found that if patients have received antibiotics, for example, the odds are low that they will produce a positive blood culture. The odds that someone will have a positive blood culture are increased, however, when there are extreme vital signs or extreme lab abnormalities.
Based on that information, Dr. Flanders said, investigators created a risk scheme that divides patients into low, moderate and high risk.
“If a patient had none of the high-risk predictors and they had received prior antibiotics,” he explained, “the physician would recommend no blood cultures. At the other extreme, if the patients had two or more of these risk factors, or they had one but they had not received antibiotics, the researchers recommended ordering two sets of blood cultures.”
If the patient was in a moderate risk group, researchers struck a compromise of sorts and ordered only one set of blood cultures. Dr. Flanders said the approach makes sense because research has shown that one set of blood cultures has the sensitivity of about 80 percent compared to two sets.
When investigators retrospectively applied this algorithm to the 13,000 patients in their study, they found that it would have likely detected 90 percent of cases of bacteremia and all the cases of fatal bacteremia. Just as importantly, the test would have done so with 40 percent fewer cultures.
Spit and sputum
Studies have shown that routine sputum analyses on hospitalized patients yield a low level of sensitivity and only a moderate level of specificity. Dr. Flanders said that the strategy rarely changes treatment, and he pointed to one study that found the test didn’t affect outcomes in hospitalized patients.
He noted that there is evidence, however, that if you target spit and sputum testing, you can greatly improve the test’s ability to detect pneumonia.
In one study that looked at sputum analyses, for example, researchers found that if the gram stain was unrevealing, so was the culture. They concluded that it makes sense to start with a gram stain, because the culture will probably not be useful if the gram stain is negative.
Dr. Flanders said research has also pointed to the importance of paying attention to gram stains that indicate pneumococcus. “In patients who have pneumococcus on gram stain,” he said, “it’s very specific. You might be able to target treatment in this small subset of patients.”
He cited another study that found when all patients were screened for sputum, the results were not impressive. When patients had received no prior antibiotics and produced a good sample, however, it was possible to identify an organism in nearly 90 percent of cases. “The test becomes a bit more impressive when you target it,” Dr. Flanders said.
Why bother with sputum?
Dr. Flanders noted research looking at the value of spit and sputum samples raises a good question: Why even bother with sputum?
“We’ve been looking at this for several decades,” Dr. Flanders acknowledged, “and the results are not overly impressive, so why the continued focus? I think part of the answer is that we are starting to see some very scary things with community-acquired pneumonia.”
The resurgence of interest in sputum testing, he said, is being spurred in part by the growing number of drug-resistant cases of MRSA, which don’t respond to empiric therapy when physicians try to treat a bug.
Dr. Flanders presented recent data from the CDC showing four cases of community-acquired MRSA in relatively young people with no risk factors. They presented with very serious disease and quickly developed cavitary lung disease.
He said that surveillance data have shown that these cases are on the rise. “That’s really making us re-think the mantra of the last 10 or 15 years that says treat and don’t test,” Dr. Flanders explained.
That’s largely why the new push for diagnostic tests is focusing on how therapy can be better tailored to individual patients.
“We are learning a little bit more every year how to better target our tests,” Dr. Flanders explained. “This is most likely to affect treatment when the unusual is suspected or when you have sicker patients.”
Edward Doyle is Editor of Today’s Hospitalist.